A4- Thyroid and Adrenal Disease Flashcards
The lobes of the thyroid contain _______ , the functional units of the thyroid gland.
•Interspersed between the follicles are __ cells, which secrete calcitonin.
The lobes of the thyroid contain follicles, the functional units of the thyroid gland.
•Interspersed between the follicles are C cells, which secrete calcitonin.
- Follicles consist of a layer of epithelium
- Central cavities containing ____
- Major constituent of colloid is the large _________, ________
- Follicular cells are ____ dependent
- Follicles consist of a layer of epithelium
- Central cavities containing colloid
- Major constituent of colloid is the large glycoprotein, thyroglobulin
- Follicular cells are TSH dependent
What is the Synthesis, Storage and Secretion of thyroid hormones
- Tyrosine and iodine are essential for synthesis of thyroid hormones.
- Both are taken up by the blood
- Tyrosine is synthesised by the body (in the thyroglobulin).
- Iodine is a dietary essential.
- Other endocrine glands secretes their hormones once produced, the thyroid gland stores considerable amount of the thyroid hormones in the colloid until needed.
Steps in biosynthesis, storage
and secretion of thyroid
hormones
- Thyroglobulin produced by follicular cells and released into colloid in follicle lumen by exocytosis
- Iodide (I-) uptake by follicular cell from the blood, oxidation (I) and transferred to colloid
- Attachments of iodine into tyrosine residues on thyroglobulin in colloid forming di-and mono-iodotyrosine (DIT and MIT)
- Coupling processes between the iodinated tyrosine molecules to form T4 (2DIT) and T3 (DIT + MIT)
• Secretion (upon stimulation) of T4 and T3
occurs by endocytosis, fusion with a lysosome, uncoupling of T4 and T3 and diffusion out of the follicular cell into the blood and onto peripheral tissues
Explain Thyroid hormone
biosynthesis
- Approximately, 90% of the hormones released from the thyroid gland initially appear in the form of T4.
- However, a majority of the T4 that is secreted from the thyroid gland is subsequently converted to T3.
- T3 is formed from monodeiodination of T4 in the thyroid and in peripheral tissues.
- T3 is 4 times more potent in its biologic form than T4 and is the major hormone that interacts with the target cells.
Clinical features of thyrotoxicosis?
- Weight loss
- Sympathetic overactivity
- Goitre
- Thyroid eye signs
Causes of thyrotoxicosis?
- Graves’ disease
- Toxic adenoma
- Multi-nodular goitre
Medical and surgical management?
Medical
• Anti-thyroid medication (carbimazole, PTU)
• Beta-blockade
Surgical
• Sub-total thyroidectomy
• Total thyroidectomy
Radioiodine
Symptoms of Hypothyroidism
- Fatigue
- Lethargy
- Weakness
- Cold intolerance
- Mental slowness
- Depression
- Dry skin
- Constipation
- Muscle cramps
- Irregular menses
- Infertility
- Mild weight gain
- Fluid retention
- Hoarseness
Signs of Hypothyroidism
- Goitre (primary hypothyroidism only)
- Bradycardia
- Non-pitting edema
- Dry skin
- Delayed relaxation
- Hypertension
- Slow speech
- Slow movements
- Voice hoarseness
Causes of Hypothyroidism
- Autoimmune (Hashimoto’s) thyroiditis
- Atrophic (common in elderly)
- Iodine 131 treatment
- pituitary
Antibodies in hypothyroidism
Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg )
antibodies (Hashimoto’s)
Hypothyroidism: Therapy
what do you use?
L-Thyroxine (levothyroxine; T4)
Goals of replacement
• Alleviate symptoms
• Titrate T4 intake to normalize TSH (primary
hypothyroidism) or free T4 (secondary and tertiary
hypothyroidism)
What is Thyroid Storm
Thyroid storm can be thought of as a “hyper-adrenergic” state, and many
of the symptoms of thyroid storm (hypertension, tachycardia,
palpitations, agitation, etc.) are best controlled with beta-blockade.
Clinical Presentation of thyroid storm
Anxiety, restlessness, agitation, psychosis, confusion, obtundation, coma.
• Thyrotoxic myopathy
• Cardiovascular abnormalities include
-tachycardia, AF
-CHF
• GI symptoms
-Pre-event severe weight loss
-Hyperdefecation, diarrhea
-Anorexia, N/V
Treatment of Thyroid Storm
Generally supportive:
• ABC’s, intubation for comatose patient
• IV fluids: Fluid resuscitation may be required in those with
volume depletion.
• Antipyretics prn
• Treat congestive failure/pulmonary edema per protocol: Diuretics
or digoxin may be required in patients with cardiac manifestations
• Treatment of any underlying precipitating factors
Management of thyroid storm
Thyroid based therapies
- Beta-blockade
- Inhibition of thyroid hormone synthesis: anti-thyroid drugs (PTU)
- Inhibition of thyroid hormone release (Lugol’siodine)
- Block peripheral conversion of T4 to T3:
• Dexamethasone 10 mg every 6 hours or hydrocortisone 100 mg
every 8 hours.
What is hypothyroidsima?
Hypothyroidism Chronic systemic disorder characterized by progressive slowing
of all bodily functions because of thyroid hormone deficiency.
❖Primary Intrinsic failure of the thyroid gland
❖Secondary Disease of the hypothalamus and/or pituitary gland
Myxedema Refers to?
severe hypothyroidism. Non-pitting, dry, waxy swelling of
the skin and SC tissue
What is
Myxedema Coma
Rare complication of hypothyroidism. Usually occurs in elderly
women, during the winter as a result of stress.
Myxoedema Coma
Clinical features
Altered mental status, confusion, pyschosis
Coma, 25 % seizures
Hypothermia: temp <35 oC
Bradycardia
Respiratory failure with CO2
retention
Hypoglycaemia
Cause of Myxoedema Coma
Drugs: sedatives, tranquillizers
Infection
Cerebrovascular accident
Trauma
Myxoedema Coma
Investigations
Hyponatraemia
Hypoglycaemia
Anaemia
Raised CK
High TSH/low T4
Cortisol
↓pO2 ↑ pCO2
Blood and urine cultures
Myxoedema Coma
Treatment
Rewarm (space blanket)
Correct BP
Adequate ventilation
Broad spectrum antibiotics
Hydrocortisone 100mg IV tds
IV T3 5-20 mcg daily for 3 days
T4 25mcg daily
Adrenal cortical layers and what do they secrete?
Adrenal Cortex: Steroid Hormone Production
Presentation of adrenal disease
•Hypofunction
•Hyperfunction:
• Cushings’ syndrome
• Conn’s syndrome
• Androgenisation
•Adrenal nodules/adenomas/masses
Adrenal Deficicency: Causes
• Primary adrenal insufficiency
–chronic: undiagnosed or established and subjected to a major physiologic stress
–acute: bilateral adrenal hemorrhage, sepsis (Waterhouse-Friederichsensyndrome)
•Secondary or tertiary adrenal insufficiency
–Less common as renin-angiotensin-aldosterone axis intact
• Exogenous glucocorticoids
When is it Adrenal deficiency/crisis
- Low Na
- High K
- Raised urea
- Low glucose
- Low random cortisol
- Synacthen test
Causes of Cushing’s syndrome
Endogenous Causes vs Exogenous Causes
Endogenous Causes
• 65% = pituitary
• 25% = adrenals
• 10% = ectopic source (small cell lung ca), non-pituitary, ACTH producing tumour
Exogenous Causes
• Iatrogenic Steroids (Asthma, RA, palliative)
Higher incidence in people with: DM, HTN, Obesity and Osteoporosis
Symptoms & Signs Cushings
Differential Diagnosis: It’s not always Cushing’s
Pseudo-Cushing’s
- Chronic severe anxiety and/or depression
- Prolonged excess alcohol consumption
- Obesity
- Poorly controlled diabetes
- HIV infection
Diagnosis of Cushing’s Syndrome
•Obtain a careful history to exclude exogenous glucocorticoid use.
•Perform at least two first-line biochemical tests to obtain the
diagnosis:
• Urine free cortisol (UFC) (at least two measurements)
• 1-mg overnight Dexamethasone Suppression Test (ODST)
• Longer low-dose Dexamethasone Suppression Test (LDDST) (2 mg/d for 48 h)
Dexamethasone Suppression Test
Explain results
Overnight Low dose = Baseline reading, Dex 1mg given at 11pm, measure cortisol at 9am
• If cortisol low (<50nmol/L) = normal
• If cortisol high (>50nmol/L) = investigate further –Cushing’s syndrome
Ix for cushings?
If any positive - imaging:
•CT of adrenals
•MRI pituitary
•IPSS (inferior petrosal sinus sampling)
If ?ectopic:
•CXR
•CT =/- MRI of neck, thorax, abdomen
•Functional imaging
Management for cushings
Drug therapy remains very important for normalising cortisol levels. Medical treatment
can also be used in patients who are unwilling or unfit for surgery.
• Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly
inhibiting synthesis and secretion in the adrenal gland.
• The treatment of choice in most patients is surgical but the metabolic consequences
increase the risk of surgery:
• increased tissue fragility
• poor wound healing
• HTN and DM
Surgical Treatment for cushings?
Pituitary tumours:
• trans-sphenoidal microsurgery.
• Radiation therapy may be used as an adjunct for patients who are not cured.
• Bilateral adrenalectomy may be necessary with severe hypercortisolaemia.
Adrenocortical tumours:
• require surgical removal –can develop Nelsons Syndrome
Removal of neoplastic tissue is indicated for ectopic ACTH production
• Metastatic spread makes a surgical cure unlikely or impossible.
• Bilateral adrenalectomy may be necessary with severe hypercortisolaemia.
